title: Oroxylin A inhibits colitis-associated carcinogenesis through modulating the IL-6/STAT3 signaling pathway.
abstract: BACKGROUND
  Patients with inflammatory bowel disease, which includes ulcerative colitis and Crohn's disease, are at a significantly increased risk of developing colorectal cancer, and aberrant interleukin (IL)-6/STAT3 signaling pathway exists in both inflammatory bowel disease and inflammation-related gastrointestinal cancers. We have previously found that oroxylin A inhibited the NF-κB signaling in human colon tumor HCT-116 cells. However, whether oroxylin A could inhibit the colitis-associated carcinogenesis remains to be determined.
  
  
  METHODS
  HCT-116 cells were treated with various concentrations of oroxylin A. Expression of relative proteins of IL-6/STAT3 signaling pathway was assayed by Western blot and immunofluorescence analysis. Mouse model for colitis-associated colorectal cancer was induced by a combined treatment with 10 mg/kg azoxymethane (AOM) followed by 3 cycles of 2.5% dextran sodium sulfate in C57BL/6 mice. IL-6 and IL-1β gene expression were analyzed by quantitative real-time PCR. Expression of relative proteins was examined by immunohistochemistry and Western blot.
  
  
  RESULTS
  Oroxylin A effectively inhibited IL-6/STAT3 pathway in human HCT-116 cells, and the effect of oroxylin A was reversible. Dietary administration of oroxylin A throughout the experimental period significantly reduced the tumor burden, inhibited cell proliferation, and induced apoptosis in colon carcinomas. The expression of inflammatory cytokines IL-6 and IL-1β decreased in tumors in oroxylin A-treated mice. The IL-6/STAT3 signaling pathway was attenuated in oroxylin A-treated mice.
  
  
  CONCLUSIONS
  Our results demonstrated that oroxylin A inhibits colitis-associated carcinogenesis through modulating IL-6/STAT3 pathway in AOM/dextran sodium sulfate mouse model and in HCT-116 cells.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Fengyi
authors.initials: F
authors.lastname: Zhang
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000150:complications*; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D005419:Flavonoids; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D016264:Dextran Sulfate; D001397:Azoxymethane